chrX-101346526-T-C
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7
The NM_004085.4(TIMM8A):c.267A>G(p.Pro89=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,209,804 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0000089 ( 0 hom., 1 hem., cov: 23)
Exomes 𝑓: 0.0000018 ( 0 hom. 2 hem. )
Consequence
TIMM8A
NM_004085.4 synonymous
NM_004085.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.415
Genes affected
TIMM8A (HGNC:11817): (translocase of inner mitochondrial membrane 8A) This translocase is involved in the import and insertion of hydrophobic membrane proteins from the cytoplasm into the mitochondrial inner membrane. The gene is mutated in Mohr-Tranebjaerg syndrome/Deafness Dystonia Syndrome (MTS/DDS) and it is postulated that MTS/DDS is a mitochondrial disease caused by a defective mitochondrial protein import system. Defects in this gene also cause Jensen syndrome; an X-linked disease with opticoacoustic nerve atrophy and muscle weakness. This protein, along with TIMM13, forms a 70 kDa heterohexamer. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Mar 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -7 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.56).
BP6
?
Variant X-101346526-T-C is Benign according to our data. Variant chrX-101346526-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1582552.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-0.415 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TIMM8A | NM_004085.4 | c.267A>G | p.Pro89= | synonymous_variant | 2/2 | ENST00000372902.4 | |
TIMM8A | NM_001145951.2 | c.*1861A>G | 3_prime_UTR_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TIMM8A | ENST00000372902.4 | c.267A>G | p.Pro89= | synonymous_variant | 2/2 | 1 | NM_004085.4 | P1 | |
TIMM8A | ENST00000644112.2 | c.*1861A>G | 3_prime_UTR_variant | 2/2 | |||||
TIMM8A | ENST00000647480.1 | n.784A>G | non_coding_transcript_exon_variant | 2/2 | |||||
TIMM8A | ENST00000645279.1 | c.*461A>G | 3_prime_UTR_variant, NMD_transcript_variant | 3/3 |
Frequencies
GnomAD3 genomes ? AF: 0.00000892 AC: 1AN: 112143Hom.: 0 Cov.: 23 AF XY: 0.0000291 AC XY: 1AN XY: 34313
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GnomAD4 exome AF: 0.00000182 AC: 2AN: 1097661Hom.: 0 Cov.: 31 AF XY: 0.00000551 AC XY: 2AN XY: 363301
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 08, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at